Effect Of Riboflavin Deficiency Research Articles

Effect of riboflavin deficiency on development of the cerebral cortex in Slc52a3 knockout mice

Riboflavin transporter 3 (RFVT3), encoded by the SLC52A3 gene, is important for riboflavin homeostasis in the small intestine, kidney, and placenta. Our previous study demonstrated that Slc52a3 knockout (Slc52a3−/−) mice exhibited neonatal lethality and metabolic disorder due to riboflavin deficiency. Here, we investigated the influence of Slc52a3 gene disruption on brain development using Slc52a3−/− embryos. Slc52a3−/− mice at postnatal day 0 showed hypoplasia of the brain and reduced thickness of cortical layers. At embryonic day 13.5, the formation of Tuj1+ neurons and Tbr2+ intermediate neural progenitors was significantly decreased; no significant difference was observed in the total number and proliferative rate of Pax6+ radial glia. Importantly, the hypoplastic phenotype was rescued upon riboflavin supplementation. Thus, it can be concluded that RFVT3 contributes to riboflavin homeostasis in embryos and that riboflavin itself is required during embryonic development of the cerebral cortex in mice.

Cytokinetic and structural responses of the rat small intestine to riboflavin depletion

Abstract:The impaired absorption and metabolism of Fe seen in riboflavin defiaency is attributed, at least in part, to a hyperproliferative response in the small intestine, associated with an altered morphology. Studies were conducted in female weanling Wistar rats to explore further the effect of riboflavin deficiency on the cytokinetics and structure of the small intestine. Feeding a riboflavin-deficient diet for 8 weeks from weaning resulted in a significantly lower villus number, a significant increase in villus length and an increased rate of transit of enterocytes along the villi, compared with weight-matched controls. A second experiment focused on the 3 weeks after weaning and showed that riboflavin deficiency inhibits the increase in villus number observed in control animals over this period. We suggest that riboflavin deficiency induced at weaning impairs the normal increase in villus number and that prolonged deficiency leads to an adaptive increase in length of villi and depth of crypts.

Riboflavin Deficiency and the Function and Fluidity of Rat Erythrocyte Membranes

The effect of riboflavin deficiency on the fluidity and function of the red blood cell (RBC) membrane and on the activity of some enzymes involved in antioxidant defense mechanisms was studied. Growing male rats were fed an experimental (riboflavin-deficient) or a control (riboflavin-supplemented) diet. Following 7 wk of feeding, RBC from riboflavin-deficient rats contained higher levels of peroxidation products, most likely due to decreased glutathione reductase activity. An elevation in glutathione peroxidase activity was also observed whereas the activity of catalase and superoxide dismutase was not affected. Membrane fluidity was studied by fluorescence polarization, using 1,6-diphenyl-1,3,5 hexatriene (DPH) as a probe. The fluidity of RBC membranes isolated from riboflavin-deficient rats was significantly lower than that of the controls. This decreased fluidity was accompanied by an increase in the activity of the membrane-bound enzyme acetylcholinesterase. This study demonstrated that a decrease in cells' ability to cope with peroxidative damage as a result of riboflavin deficiency may lead to changes in the fluidity and function of membranes.

Skin wound healing in riboflavin deficiency

Healing of excision and incision wounds was evaluated in riboflavin-deficient rats. The period taken for the epithelialization of excision wounds was 4 to 5 days longer in riboflavin-deficient animals compared to ad libitum-fed or food-restricted weight-matched control groups. Riboflavin deficiency as well as food restriction slowed the rate of wound contraction, the effect of riboflavin deficiency being of greater magnitude. The tensile strength of incision wounds in riboflavin deficiency was reduced to 42% of the ad libitum-fed control and 63% of the weight-matched control values. There was a decrease of 25% in total collagen content of incision wounds, in riboflavin deficiency and its maturity was drastically affected as indicated by a twofold increase in salt solubility (1 m NaCl) and a four-fold increase in the α β subunit ratio of salt-soluble collagen. Food restriction had similar effects but of lower magnitude. The data suggest that alteration in collagen content and maturity may be responsible for the lower tensile strength of incision wounds in riboflavin-deficient rats. This suggestion was supported by the results of a rehabilitation experiment.

Effect of riboflavin deficiency on sorbitol pathway in rat lens

The sorbitol pathway comprising of NADPH dependent aldose reductase (AR) and NAD + dependent sorbitol dehydrogenase (SDH) which convert glucose to sorbitol and then to fructose, respectively was studied in riboflavin deficient rat lens. The activities of AR and SDH were increased significantly in lenses from riboflavin deficient rats as compared to both ad libitum and pair-fed control groups of rats. While the ratio of NADPH to NADP +, and the levels of NADPH were also increased significantly in the riboflavin deficient rat lenses over the riboflavin supplemented (both ad libitum and pair-fed) rat lenses, the levels of total pyridine nucleotides (NADPH+NADP +) in deficient rat lenses were significantly higher than those from ad libitum controls alone. There were, however, no significant differences in the levels of sorbitol among the three groups of rats. The data suggest that the sorbitol pathway is enhanced in rat lens during riboflavin deficiency.

The effect of riboflavin deficiency on cerebrum and cerebellum of developing rat brain.

After 21-day-old weanling rats were maintained on diets deficient in riboflavin the weights of their brains were 19.8% less than those of rats on control diets. In riboflavin deficiency, the myelin lipids, cerebrosides, and sphingomyelin, as well as phosphatidylethanolamine, a significant component of the myelin membrane, were considerably reduced in proportion. It is considered that riboflavin plays some role in the metabolism of essential fatty acids in brain lipids and the pathological effect of its deficiency is similar to that of essential fatty acid deficiency, causing a fast impairment to brain development and maturation.

Transport of riboflavin-binding protein to the hen oocyte: Bound vitamin is not required for protein deposition

The effect of riboflavin deficiency on the deposition of riboflavin-binding protein in chicken egg yolk and albumen was studied. Laying hens were fed either a riboflavin-deficient (.44 μg/g) or supplemented (9.5 μg/mg) diet and their plasma, egg yolk and albumen were assayed for the concentrations of riboflavin-binding protein and riboflavin by radioligand binding and isotope dilution. Riboflavin deficiency did not affect riboflavin-binding protein concentrations, but did decrease the proportion of protein that contained bound riboflavin in yolk and albumen. Thus, bound riboflavin is not required for deposition of riboflavin-binding protein into the developing oocyte, nor does riboflavin modulate synthesis or secretion of riboflavin-binding protein. In a second experiment, daily yolk deposition was monitored by force-feeding hens lipid- soluble dyes which were deposited in the developing oocyte and served as markers. The individual yolk rings were assayed for riboflavin-binding protein and riboflavin. These experiments showed that riboflavin-binding protein deposition is continuous throughout oocyte development, whereas the ratio of riboflavin to riboflavin-binding protein decreases gradually to near zero after transfer of the hen to a riboflavin-deficient diet. If oocyte deposition of riboflavin-binding protein is receptor-mediated, bound riboflavin is not required for the recognition and transport processes.

The effect of riboflavin deficiency in rats on the absorption and distribution of iron

1. Riboflavin may play a part in the transport of iron across the gastrointestinal mucosa. Fe absorption was measured in the rat by monitoring whole-body retention of a dose of 59Fe using a small-animal gamma-counter. 2. Female Norwegian Hooded rats were fed on a diet deficient in riboflavin (B2-) from 5 weeks of age. Control animals, fed on a complete diet (B2+), were weight-matched to rats fed on the B2- diet. After 7 weeks all rats were fed on a test meal extrinsically labelled with 59Fe and whole-body radioactivity measured for 15 d. 3. Riboflavin deficiency was associated with a reduction in the percentage of the dose absorbed and an increase in the rate of loss of Fe post absorption. 4. A smaller percentage of the absorbed dose was present in the livers of the riboflavin-deficient animals.

Effect of riboflavin deficiency on lipid metabolism of liver and brown adipose tissue of sucking rat pups.

An increase in liver: body-weight and in hepatic triacylglycerol content, together with changes in the fatty acid profiles of hepatic phospholipids, were observed as a result of moderate riboflavin deficiency in sucking rat pups. Oxygen consumption by hepatic mitochondria, with palmitoyl L-carnitine as substrate, was not significantly impaired. Mitochondria from interscapular brown adipose tissue, however, showed a marked impairment of O2 consumption, with palmitoyl L-carnitine as substrate, in the riboflavin-deficient pups. This impairment was also apparent after uncoupling with carbonyl cyanide p-trifluoromethoxyphenylhydrazone, but was not consistently observed after the addition of GDP to suppress uncoupled oxidation. It was much less evident, and did not reach statistical significance, for the mitochondria of brown adipose tissue of the corresponding deficient dams. Binding of 3H-labelled GDP by brown adipose tissue mitochondria was unaffected by riboflavin deficiency in the pups, suggesting that the effect on O2 consumption is more likely to be due to impaired integrity of the mitochondrial respiratory chain, than to impairment of the specific capacity for uncoupling of respiration which is characteristic of brown adipose tissue mitochondria. Total cytochrome c oxidase (EC 1.9.3.1) activity of the brown adipose tissue of riboflavin-deficient pups was not significantly reduced. A small but significant impairment was observed in the stimulation of whole-body O2 consumption by injected noradrenaline in the riboflavin-deficient pups, suggesting that the impairment of brown adipose tissue mitochondrial function may be accompanied by impaired physiological capacity in vivo.

Effect of riboflavin deficiency on reproductive performance and on biochemical indices of riboflavin status in the rat.

Young female rats were made riboflavin-deficient by feeding a purified diet containing casein (210 g/kg). This basal diet provided 0.40 mg riboflavin/kg diet, to which was added additional riboflavin at 0, 0.12 or 0.25 mg/kg diet. Control animals received the same diet with 15 mg added riboflavin/kg. The diets were given for 4 weeks before mating, then throughout pregnancy and for 15 d of lactation. With no added riboflavin in the diet, reproduction was severely impaired and fetal resorption was usually observed. With 0.12 mg added riboflavin/kg diet, however, reproduction was usually successful, and the growth of dams and pups was only marginally depressed in comparison with pair-fed controls optimally supplied with riboflavin. The activation coefficient (stimulated:basal activity) of erythrocyte glutathione reductase (NAD(P)H) (EC 1.6.4.2) was high, and the concentration of riboflavin in the liver was correspondingly low in the dams receiving diets containing 0.12 or 0.25 mg added riboflavin/kg and in their sucking pups at 15 d post partum. Riboflavin levels in the milk from both groups of dams were about eightfold lower than in controls. There was little evidence that the sucking pups could maintain their riboflavin level at the expense of that in the maternal tissues.

L-gulonolactone oxidase activity and vitamin C status in riboflavin-deficient rats

The effect of riboflavin deficiency on the activity of L-gulonolactone oxidase [ L-gulono-γ-lactone : oxygen 2-oxidoreductase, EC 1.1.3.8] and on vitamin C status was studied. A marked decrease in the specific activity of L-gulonolactone oxidase was observed in the liver microsomes isolated from riboflavin-deficient rats: the specific activity was approx. one-third of that in the microsomes isolated from control rats. The L-ascorbic acid content in the liver of the riboflavin-deficient rats was approx. one-half of that in the liver of the control rats. It seems that the rate of production of L-ascorbic acid in the riboflavin-deficient rats is limited by the decreased level of L-gulonolactone oxidase activity. Immunotitration using rabbit antiserum directed to L-gulonolactone oxidase revealed that a substantial amount of an inactive form of this enzyme is present in the liver microsomes of the riboflavin-deficient rats. L-Gulonolactone oxidase activity in the microsomes of these rats increased by approx. 35% upon addition of FAD, but it was slightly decreased by the addition of FMN or riboflavin. These results indicate that the liver microsomes of the riboflavin-deficient rats contain a protein which exhibits L-gulonolactone oxidase activity upon addition of FAD.

Effect of riboflavin deficiency on activity of NADH-FMN oxidoreductase (ferriductase) and iron content of rat liver.

Conference Article| February 01 1977 Effect of Riboflavin Deficiency on Activity of NADH-FMN Oxidoreductase (Ferriductase) and Iron Content of Rat Liver ZAHUR ZAMAN; ZAHUR ZAMAN 1Department of Medical Research, Catholic University of Leuven, Kapucijnen Voer 35, B-3000 Leuven, Belgium Search for other works by this author on: This Site PubMed Google Scholar ROBERECHT L. VERWILGHEN ROBERECHT L. VERWILGHEN 2Department of Medical Research, Catholic University of Leuven, Kapucijnen Voer 35, B-3000 Leuven, Belgium Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1977) 5 (1): 306–308. https://doi.org/10.1042/bst0050306 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share MailTo Twitter LinkedIn Cite Icon Cite Get Permissions Citation ZAHUR ZAMAN, ROBERECHT L. VERWILGHEN; Effect of Riboflavin Deficiency on Activity of NADH-FMN Oxidoreductase (Ferriductase) and Iron Content of Rat Liver. Biochem Soc Trans 1 February 1977; 5 (1): 306–308. doi: https://doi.org/10.1042/bst0050306 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1977 Biochemical Society1977 Article PDF first page preview Close Modal You do not currently have access to this content.

Hepatic drug hydroxylation and lipid peroxidation in riboflavin-deficient rats.

The effect of riboflavin deficiency and phenobarbital pretreatment on drug hydroxylation and lipid peroxidation was investigated. A significant decrease in aniline and acetanilide hydroxylation as well as NADPH-linked and ascorbate-induced lipid peroxidation was observed during 4- and 7-week riboflavin deficiency in both adult male and adult female rats. The drug-hydroxylation and lipid-peroxidation activities were further lowered with the increase in riboflavin deficiency. The phenobarbital pretreatment induced aniline and acetanilide hydroxylase activity even in riboflavin-deficient animals. Drug hydroxylation inhibits lipid peroxidation in both deficient and normal rats. The administration of riboflavin was followed by a significant increase in drug hydroxylation and lipid peroxidation.

Effect of riboflavin deficiency on phenobarbital and 3-methylcholanthrene induction of microsomal drug-metabolizing enzymes of the rat

The effect of riboflavin deficiency on the induction of hepatic microsomal enzymes by phenobarbital and 3-methylcholanthrene has been investigated. A decrease in microsomal flavin levels of 56 per cent was associated with a decrease in NADPH cytochrome c reductase (52 per cent), azoreductase (71 per cent) and benzpyrene hydroxylase (74 per cent). Microsomal cytochrome P-450 content and aminopyrine demethylase were not significantly affected by flavin deficiency. Phenobarbital or 3-methylcholanthrene pretreatment did not affect hepatic microsomal flavin levels in normal or deficient animals. In flavin-deficient animals, phenobarbital pretreatment significantly increased cytochrome c reductase, cytochrome P-450 content, aminopyrine demethylase and azoreductase. Thus the carbon monoxide-sensitive pathway (cytochrome P-450 mediated) of azoreductase was essentially unaffected by flavin deficiency. In deficient animals, the carbon monoxide-insensitive microsomal azoreductase pathway (non-cytochrome P-450 mediated) normally induced by 3-methylcholanthrene was unaffected. Thus, induction of azoreductase by 3-methylcholanthrene was found to be flavin dependent. However, 3-methylcholanthrene did increase cytochrome P-450 content and benzpyrene hydroxylase in flavin-deficient animals. The induction of benzpyrene hydroxylase by 3-methylcholanthrene increased with increasing microsomal flavin content. Part of the mechanism of azoreductase induction by 3-methylcholanthrene was due to an induced change in the structure or composition of microsomal flavoprotein. This interpretation is supported by the findings that: (1) induction by 3-methylcholanthrene in riboflavin-deficient rats required a minimal flavin level, (2) increased enzyme activity was not compensated by an increase in microsomal flavin and (3) induction by 3-methylcholanthrene augmented FMN-stimulation of microsomal azoreductase in vitro.

Phospholipid and protein metabolism in mouse liver mitochondria during riboflavin deficiency and recovery.

A study was made of the effect of riboflavin deficiency and recovery upon the structure and function of mitochondrial membranes in mouse liver. In the deficient animals the mitochondria were enlarged and contained reduced numbers of inner membrane profiles. The activity of enzymes of the inner membranes (succinate cytochrome c reductase, cytochrome oxidase) was reduced in the deficient mitochondria, as was the content of diphosphatidylglycerol, an inner membrane phospholipid; monoamine oxidase, a mitochondrial outer membrane enzyme, and the coupling reactions of oxidative phosphorylation did not appear to be affected. Incorporation in vivo of 32Pi into phospholipids and of 3H-leucine into proteins of deficient mitochondria was normal or somewhat enhanced. Following the administration of riboflavin to the deficient mice, liver mitochondria appeared to undergo division, and inner membrane profiles seemed more numerous. Riboflavin administration increased the 3H labelling of tightly bound mitochondrial proteins, and decreased the 32P labelling of the phosphatidylcholine fraction.

The effect of riboflavin deficiency on key gluconeogenic enzyme activities in rat liver.

The sequel of riboflavin deficiency, as it is now known, may be initiated by a selective decrease in the activity of several fiavoproteins involved in cellular oxidation (1–3). This in turn may aff...

Effect of riboflavin deficiency on metabolism of the rat in hyperthyroid and euthyroid state

The basal metabolic rate in riboflavin-deficient rats is lowered. Upon application of triiodothyronine, oxygen consumption is raised to the level of the thyrotoxic controls. Activity levels of flavin enzymes [α-glycerolphosphate dehydrogenase ( l-glycerol-3-phosphate:(acceptor) oxidoreductase, EC 1.1.99.5), succinate dehydrogenase (succinate:(acceptor) oxidoreductase, EC 1.3.99.1), monoamine oxidase (monoamines:O 2 oxidoreductase (deaminating), EC 1.4.3.4)] were determined in liver, musculus rectus femoris, musculus soleus, heart muscle, and cortex cerebri. Riboflavin deficiency causes a decrease of α-glycerolphosphate dehydrogenase in liver, musculus rectus femoris, and heart muscle and a decrease of succinate dehydrogenase and monoamine oxidase primarily in liver. The induction of α-glycerolphosphate dehydrogenase by triiodothyronine is abolished in deficient animals. It is proposed that under riboflavin deficiency a lower level of thyroid hormones is responsible for the decreased metabolic rate and that the decreased activities of flavin enzymes are not rate limiting.

Effect of protein depletion and subsequent repletion on in vivo incorporation of ( 14 C) amino acid into rat liver proteins in riboflavin deficiency.

The effect of riboflavin deficiency on in vivo incorporation of [1-14C] leucine into proteins of liver has been studied on rats following protein depletion and subsequent repletion.The increase in the incorporation of [14C] amino acid into liver proteins following protein depletion was less marked in riboflavin-deficient rats. But repletion with 40% protein demonstrated marked diminished protein incorporation in riboflavin-deficient rats compared to pair-fed control rats.Riboflavin deficiency does not show any alteration in the liver protein concentration following any of the dietary treatments.It is concluded that there occurs less synthesis and diminished rate of breakdown of liver proteins in riboflavin deficiency following protein depletion, and repletion with high protein diet following protein depletion causes diminished protein synthesis as well as reduced protein breakdown in liver of riboflavin-deficient rats and consequently liver protein concentration remains unchanged.

Effect of riboflavin deficiency on the metabolism of oxypurines in chicks.

Day-old broiler chicks of both sexes were used in three experiments to determine the effect of riboflavin deficiency on oxypurine metabolism catalyzed by xanthine dehydrogenase, a riboflavin-containing enzyme. Chicks fed a riboflavin-deficient diet (1.38 mg/kg) for 3 weeks exhibited depressed growth and a high incidence of curled-toe paralysis (higher than 80%) as compared to control chicks (15.1 mg riboflavin per kilogram diet; no incidence of curled-toe paralysis). In addition, the precursors of uric acid, hypoxanthine and/or xanthine, accumulated in the liver and kidney of deficient chicks showing curled-toe paralysis. These observations show that dietary riboflavin being incorporated into xanthine dehydrogenase is essential for oxypurine metabolism. Moreover in the chick, the liver and the kidney may be important sites of uric acid synthesis. The low uric acid concentration in the plasma of the deficient chicks appeared to be indicative of a disturbance in uric acid synthesis in the liver and kidney.

Effect of ribofavin deficiency on free amino acid nitrogen concentrations of liver, muscle and plasma.

Mannliche Albino-Ratten, 45 Tage bei riboflavinarmer Nahrung, zeigten erhohten Gehalt freien Aminosaure-Stickstoffs in Leber, Muskel und Plasma. Die Erhohung scheint durch eine gesteigerte Aktivitat der Nebennierenrinde beim Riboflavinmangel herbeigefuhrt zu sein.